Synthesis, antimicrobial activity and acid dissociation constants of methyl 5,5-diphenyl-1-(thiazol-2-yl)pyrrolidine-2-carboxylate derivatives
Nural, Yahya | Gemili, Muge | Ulger, Mahmut
In this study, a series of polysubstituted methyl 5,5-diphenyl-1-(thiazol-2-yl)pyrrolidine-2-carboxylate derivatives were designed and synthesized by the cyclization reaction of methyl 1-(benzoylcarbamothioyl)-5,5-diphenylpyrrolidine-2-carboxylates and 2-bromo-1-(4-substituted phenyl) ethanones in 70-96% yield. The starting pyrrolidine derivatives were synthesized via a 1,3-dipolar cycloaddition reaction in 83-88% yield. The stereochemistry of one of these methyl 5,5-diphenyl-1-(thiazol-2-yl)pyrrolidine-2-carboxylate derivatives was characterized by a single crystal X-ray diffraction study and the acid dissociation constants of these compounds were determined. An antimicrobial screening was performed against different bacterial and fungal strains and against the M. tuberculosis H37Rv strai...
Synthesis, crystal structure, DFT studies, acid dissociation constant, and antimicrobial activity of methyl 2-(4-chlorophenyl)-7a-((4-chlorophenyl)carbamothioyl)-1-oxo-5,5-diphenyl-3-thioxo-hexahydro-1H-pyrrolo[1,2-e]imidazole-6-carboxylate
Nural, Yahya | Gemili, Muge | Ulger, Mahmut
A novel bicyclic thiohydantoin fused to pyrrolidine compound, methyl 2-(4-chlorophenyl)-7a-((4-chlorophenyl)carbamothioyl)-1-oxo-5,5-diphenyl-3-thioxo-hexahydro-1H-pyrrolo[1,2-e]imidazole-6-carboxylate, was synthesized by the cyclization reaction of dimethyl 5,5-diphenylpyrrolidine-2,4-dicarboxylate and 4-chlorophenyl isothiocyanate in the presence of 4-(dimethylamino)pyridine to form methyl 2-(4-chlorophenyl)-1-oxo-5,5-diphenyl-3-thioxo-hexahydro-1H-pyrrolo[1,2-e]imidazole-6-carboxylate with concomitant addition reaction of the 4-chlorophenyl isothiocyanate in 79% yield. The structural characterization was performed by NMR, FT-IR, MS and HRMS techniques, and the stereochemistry of the compound was determined by single crystal X-ray diffraction study. In addition, the molecular structure a...
Novel highly functionalized 1,4-naphthoquinone 2-iminothiazole hybrids: Synthesis, photophysical properties, crystal structure, DFT studies, and anti(myco)bacterial/antifungal activity
Gemili, Muge | Nural, Yahya | Ülger, Mahmut | Erat, Selma
In this paper, a series of novel highly functionalized 1,4-naphthoquinone 2-iminothiazole hybrids were synthesized via a cyclization reaction of 2,3-diaminonaphthalene-1,4-dione N-aroylthioureas and alpha-bromoketones in good to excellent yields (74-94%). The stereochemistry of one of the 1,4-naphthoquinone 2-iminothiazole products was characterized by single crystal X-ray diffraction technique. Photophysical properties of the compounds in DMSO, HAc and THF were determined by using UV-vis spectroscopy. The ground state geometries and the absorption spectra of the compounds were also determined using Density Functional Theory (DFT) and time-dependent DFT (TD-DFT) at B3LYP/631 + g(d,p) level of theory. The computed results are consistent with experimental values. An antimicrobial screening w...
Pt(II) and Ni(II) complexes of octahydropyrrolo[3,4-c]pyrrole N-benzoylthiourea derivatives: Synthesis, characterization, physical parameters and biological activity
Gemili, Muge | Ulger, Mahmut | Nural, Yahya
In this study, four novel Pt(II) and Ni(II) complexes of octahydropyrrolo[3,4-c]pyrrole, consisting of pyrrolidine fused to pyrrolidine-2,5-dione, N-benzoylthiourea derivatives were synthesized and their structural characterization was performed by NMR, FT-IR, MS, HRMS and elemental analysis techniques and single crystal X-ray diffraction studies. The octahydropyrrolo[3,4-c]pyrrole N-benzoylthiourea compound 3c crystallizes triclinic, with space group P-1. Pt(II) and Ni(II) ions created cis-complexes Pt(II) 4c and Ni (II) 5a forming distorted square-planar structures in orthorhombic space groups Pnma and Pbca, respectively. Furthermore, the ligands behave as bidentate and bind to the metal atom via the S and O atoms. Acid dissociation constants of the ligands were determined by potentiomet...
Synthesis and anti(myco)bacterial activity of novel 5,5-diphenylpyrrolidine N-aroylthiourea derivatives and a functionalized hexahydro-1H-pyrrolo[1,2-c]imidazole
Ersen, Duygu | Ulger, Mahmut | Gemili, Muge | Nural, Yahya
In this paper, five novel 5,5-diphenylpyrrolidine N-aroylthiourea derivatives were synthesized by stereoselective cycloaddition of N-diphenylmethylene-protected glycine methyl ester and methyl acrylate, and subsequent coupling with aroylisothiocyanates. The cis-stereochemistry of one of the heterocyclic thiourea derivatives was characterized by single crystal X-ray diffraction studies. The compounds showed antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Aeromonas hydrophila, Escherichia. coli and Acinetobacter baumannii with minimum inhibitory concentration values in the range of 62.5-1000 mu g/mL against these bacterial strains. Antimycobacterial activity of the compounds was investigated against the M. tuberculosis H37Rv strain and all compounds exhibited antimyc...
1,4-Naphthoquinone thiazole urea hybrids bearing morpholine/piperazine: synthesis, crystal structure, aldose reductase and α-glycosidase enzyme inhibition, molecular docking, and electrochemical interaction with dsDNA
Efeoglu, Cagla | Nural, Yahya
In this study, new 1,4-naphthoquinone thiazole urea hybrids bearing morpholine (3a-d) or piperazine (3e-h) moiety were synthesized in 76-89 % yields and characterized by 1H NMR, 13C NMR, FT-IR, HRMS, and elemental analysis. The stereochemistry of 3d was determined by single crystal x-ray diffraction study. We evaluated the inhibitory potential of these compounds 3a-h on aldose reductase (ALR2) and alpha-glycosidase enzyme (alpha-GLY) activity. Our results indicate that these compounds substantially inhibit ALR2 at micromolar doses, with inhibition constants (KIs) between 0.79 and 2.20 mu M and inhibit alpha-GLY KI between 0.67 and 2.82 mu M. Molecular docking simulations were utilized to elucidate inhibitory effects and establish structure-activity relationships for the synthesized compoun...
Polysubstituted Fused Ring Bicyclic Thiohydantoins from Aminocarbo-N-thioylpyrrolidines Derived from Azomethine Ylide 1,3-Dipolar Cycloadditions
Nural, Yahya | Dondas, Haci Ali
Highly substituted bicyclic thiohydantoins fused to pyrrolidines were prepared from aminocarbo-N-thioylpyrrolidines derived from alpha-amino acid esters via imine azomethine ylide 1,3-dipolar cycloadditions and subsequent reaction with aroylisothiocyanates. Aminocarbo-N-thioylpyrrolidines efficiently undergo cyclisation in the presence of sodium methoxide to form bicyclic N-substituted thiohydantoins with concomitant cleavage of the N-acyl group in good to excellent yield. And also some interesting both regiospecific and stereospecific rearrangement to the bicyclic fused thiocarbamoil pyrrolidine and bicyclic thiohydantoin were observed.
Polysubstituted pyrrolidines linked to 1,2,3-triazoles: Synthesis, crystal structure, DFT studies, acid dissociation constant, drug-likeness, and anti-proliferative activity
Ince, Tuncay | Demir, Bunyamin | Erat, Selma | Nural, Yahya
Novel pyrrolidines linked to 1,2,3-triazole derivatives, dimethyl 1-(2 (4-R-1H 1,2,3 triazol-1-yl)-acetyl)-5,5-diphenylpyrrolidine-2,4-dicarboxylate, were synthesized in the presence of sodium ascorbate and copper (II) sulfate pentahydrate by click chemistry in excellent 89-95% yield. The H-1 NMR, C-13 NMR, DEPT, COSY, HMQC, FT-IR, HRMS and elemental analysis techniques were used for structural characterization. A single crystal X-ray diffraction study was performed in order to determine the stereochemistry of the compounds. The optimization geometry of the compounds was obtained by performing density functional theory. However, the global reactivity parameters were estimated from frontier molecular orbitals. The calculated global reactivity parameters showed that the most reactive compoun...
Synthesis of novel acylthioureas bearing naphthoquinone moiety as dual sensor for high-performance naked-eye colorimetric and fluorescence detection of CN− and F− ions and its application in water and food samples
Nural, Yahya | Karasu, Elize | Efeoglu, Cagla
In this study, six new acylthiourea, bearing naphthoquinone moiety, sensors were synthesized in high yield (88-96%) and characterized using H-1/C-13 NMR, FT-IR and HRMS techniques. All synthesized sensors (4a-f) showed shifts in absorbance and colorimetric changes by CN-, F-, AcO-, and H2PO4-. However, 4e showed a chromogenic different sensitivity response to CN- and F- against competing anions such as AcO- and H2PO4- in DMSO. Furthermore, CN- added 4e showed an increase at the emission intensity and intensive fluorimetric color change was observed in UV-light (lambda ex. 365 nm). All sensors showed chromogenic selectivity towards CN- in aqueous solutions (in DMSO/H2O: 1:1, v/v). Interaction mechanisms between 4e and CN- and F- anions were investigated by experimental studies using various...